Absence of MHC-II expression by lymph node stromal cells results in autoimmunity.

How lymph node stromal cells (LNSCs) shape peripheral T-cell responses remains unclear. We have previously demonstrated that murine LNSCs, lymphatic endothelial cells (LECs), blood endothelial cells (BECs), and fibroblastic reticular cells (FRCs) use the IFN-γ-inducible promoter IV (pIV) of the MHC class II (MHCII) transactivator CIITA to express MHCII. Here, we show that aging mice (>1 yr old) in which MHCII is abrogated in LNSCs by the selective deletion of pIV exhibit a significant T-cell dysregulation in LNs, including defective Treg and increased effector CD4 <sup>+</sup> and CD8 <sup>+</sup> T-cell frequencies, resulting in enhanced peripheral organ T-cell infiltration and autoantibody production. The proliferation of LN-Tregs interacting with LECs increases following MHCII up-regulation by LECs upon aging or after exposure to IFN-γ, this effect being abolished in mice in which LECs lack MHCII. Overall, our work underpins the importance of LNSCs, particularly LECs, in supporting Tregs and T-cell tolerance

A SINE Insertion in ATP1B2 in Belgian Shepherd Dogs Affected by Spongy Degeneration with Cerebellar Ataxia (SDCA2).

Spongy degeneration with cerebellar ataxia (SDCA) is a genetically heterogeneous neurodegenerative disorder with autosomal recessive inheritance in Malinois dogs, one of the four varieties of the Belgian Shepherd breed. Using a combined linkage and homozygosity mapping approach we identified a ~10.6 Mb critical interval on chromosome 5 in a Malinois family with four puppies affected by cerebellar dysfunction. Visual inspection of the 10.6 Mb interval in whole genome sequencing data from one affected puppy revealed a 227 bp SINE insertion into the ATP1B2 gene encoding the β2 subunit of the Na(+)/K(+)-ATPase holoenzyme (ATP1B2:c.130_131insLT796559.1:g.50_276). The SINE insertion caused aberrant RNA splicing. Immunohistochemistry indicated a reduction of ATP1B2 protein expression in the central nervous system of affected puppies. Atp1b2 knock-out mice had previously been reported to show clinical and neurohistopathological findings similar to the affected Malinois puppies. Therefore, we consider ATP1B2:c.130_131ins227 the most likely candidate causative variant for a second subtype of SDCA in Malinois dogs, which we propose to term spongy degeneration with cerebellar ataxia subtype 2 (SDCA2). Our study further elucidates the genetic and phenotypic complexity underlying cerebellar dysfunction in Malinois dogs and provides the basis for a genetic test to eradicate one specific neurodegenerative disease from the breeding population in Malinois and the other varieties of the Belgian Shepherd breed. ATP1B2 thus represents another candidate gene for human inherited cerebellar ataxias, and SDCA2 affected Malinois puppies may serve as naturally occurring animal model for this disorder

Salmonella enterica subsp. diarizonae serotype 61:k:1,5,(7) associated with chronic proliferative rhinitis and high nasal colonization rates in a flock of Texel sheep in Switzerland.

Salmonella (S.) enterica subspecies diarizonae (IIIb) serovar 61:(k):1,5,(7) (S. IIIb 61:(k):1,5,(7)) is considered to be host adapted to sheep and is found regularly in feces of healthy carriers and of sheep with salmonellosis. A few cases of chronic proliferative rhinitis (CPR) in sheep have been described as a new disease in association with S. IIIb 61:k:1,5,(7) in the USA, in Spain and now for the first time in Switzerland. Three animals of a flock of Texel sheep suffering from chronic nasal discharge and dyspnea with subsequent death were necropsied. The pathological lesions are consistent with a severe proliferation of the nasal mucosae of the turbinates in association with severe chronic inflammation. S. IIIb 61:(k):1,5,(7) was isolated from the lesions by direct bacteriological culture and the presence of Salmonella spp. was confirmed by immunohistochemistry. The affected flock was systematically tested after the first occurrence of the disease. Clinical examination of the flock revealed approx. 20% of the adult sheep to show nasal discharge, approx. 5% having severe dyspnea and approx. 5% having chronic intermittent diarrhea. Lambs (n=28) showed no clinical signs at all. High positivity of nasal mucosa (46%), but low prevalence in feces (6%) for S. IIIb 61:k:1,5,(7) was found. The results lead to the assumption of a direct animal to animal transmission by nasal discharge followed by a chronic disease leading to death after several months to years. Animals tested positive for S. IIIb 61:k:1,5,(7) were all >1year old. CPR represents a chronic disease in adult sheep posing a risk for spreading S. IIIb 61:k:1,5,(7) between flocks and with a zoonotic potential

Serratospiculosis in Captive Peregrine Falcons (Falco peregrinus) in Switzerland

Infection with Serratospiculum species was identified in a captive peregrine falcon (Falco peregrinus) in Switzerland. Pathologic and parasitologic examination results revealed generalized severe granulomatous airsacculitis, with intralesional adults, larvae, and eggs of Serratospiculum species. Subsequently, an individual coprological analysis of the remaining 15 falcons (peregrine falcons and gyrfalcons [Falco rusticolus]) from the same owner was performed. Eggs of Serratospiculum species (4 birds) and Capillaria species (11 birds), and oocysts of Caryospora species (1 bird) were detected. Treatment with ivermection (2 mg/kg SC) was effective, as none of the falcons excreted Serratospiculum species eggs 10 days after one dose. To our knowledge, this is the first report of infection with Serratospiculum species in captive falcons in Europe

APOB-associated cholesterol deficiency in Holstein cattle is not a simple recessive disease.

In 2015, cholesterol deficiency (CD) was reported for the first time as a new recessive defect in Holstein cattle. After GWAS mapping and identification of a disease-associated haplotype, a causative loss-of-function variant in APOB was identified. CD-clinically affected APOB homozygotes showed poor development, intermittent diarrhea and hypocholesterolemia and, consequently, a limited life expectation. Herein, we present a collection of 18 cases clinically diagnosed as CD-affected APOB heterozygotes. CD-clinically affected heterozygotes show reduced cholesterol and triglyceride blood concentrations. The differences in total blood cholesterol and triglycerides between nine CD-clinically affected and 36 non-affected heterozygotes were significant. As only some APOB heterozygotes show the clinical CD phenotype, we assume that the penetrance is reduced in heterozygotes compared to the fully penetrant effect observed in homozygotes. We conclude that APOB-associated CD represents most likely an incomplete dominant inherited metabolic disease with incomplete penetrance in heterozygotes